Multiple MyelomaPhase 1/2NCT03773107
LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Study of CRD for Carfilzomib-Refractory Multiple Myeloma
A Phase 1/2 study testing Carfilzomib, Ruxolitinib and Dexamethasone in people with Multiple Myeloma, run by Wake Forest University Health Sciences at 2 sites in United States.
Trial summary
The primary objective of Phase I is to establish the maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and dexamethasone. The primary objective of phase II is to evaluate progression-free survival (PFS) at 4 months in multiple myeloma subjects who receive the combination treatment… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Carfilzomib, Ruxolitinib and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Jan 2019to 21 Feb 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following criteria:
- Documented history of relapsed and/or refractory multiple myeloma with > 2 lines of therapy. One of the prior lines of therapy must have been a carfilzomib containing regimen with evidence of relapse or progression within the last 60 days of the carfilzomib containing regimen with a carfilzomib dose of at least 27 mg/m2. Carfilzomib containing regimen at the standard dose of 20/27 mg/m2 is acceptable.
- Measurable disease, as defined by at least one of the following:
- Serum monoclonal protein level ≥0.5 g/dL for IgG, IgA, or IgM disease
- Urinary M-protein excretion of ≥200 mg over a 24-hour period
- Involved free light chain level ≥10 mg/dL, along with an abnormal free light chain ratio
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- Adequate bone marrow reserves, as defined by the following:
- Absolute neutrophil count (ANC) ≥1000 cells/mm3 within 1 week of the initiation of treatment
- Platelet count of ≥75 ,000 cells/mm3 for subjects who have bone marrow plasmacytosis of <50%, or ≥50,000 cells/mm3 for subjects who have bone marrow plasmacytosis of >50%
- Adequate hepatic function, as defined by the following:
- Total bilirubin ≤ 2 times the upper limit of the institutional normal values
- Total AST and ALT ≤ 3 times the upper limit of the institutional normal values
- Adequate renal function, as defined by the following: creatinine clearance (CrCl) ≥ 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula.
- Adequate cardiac function defined as LVEF ≥ 40% by MUGA, echocardiogram or cardiac MRI.
- Be 18-75 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- FOCBP and male subjects who are sexually active with FOCBP must agree to use two highly effective (as determined per the Investigator) methods of contraception during the study and for 30 days (female subjects) or for 90 days (male subjects) following the last dose of study treatment including a male condom.
- Ability to understand and the willingness to sign a written informed consent document.
- Recovered from all reversible acute toxic effects of prior therapy (other than alopecia) to ≤ Grade 1 or baseline.
Who cannot join
- Subjects must not meet any of the following criteria:
- Non-secretory multiple myeloma
- Known amyloidosis
- Known POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Clinically significant illness including, but not limited to the following: active systemic infection, uncontrolled hypertension (as defined by BP > 160/90), New York Heart Association Class III and IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months of consent, uncontrolled cardiac arrhythmia, or any other condition (including laboratory abnormalities) that, in the opinion of the Investigator, places the subject at unacceptable risk for adverse outcome if he/she were to participate in the study
- Prior cerebrovascular accident with persistent neurologic deficit.
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- Psychiatric illness/social situations that would limit compliance with study treatment and requirements
- Pregnant or breast feeding. Females of childbearing potential (FOCBP) must have a negative serum pregnancy test within the 7 days prior to study drug administration and a negative urine pregnancy test within the 3 days prior to the first study drug administration.
- Known human immunodeficiency virus (HIV) infection
- Active hepatitis B and/or hepatitis C infection
- Currently active second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Subjects are not considered to have a currently active malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for >5 years, and are considered by their physician to be at less than 30% risk of relapse. In addition, subjects with basal cell carcinoma of the skin, superficial carcinoma of the bladder, carcinoma of the prostate with a current PSA value of <0.5 ng/mL, or cervical intraepithelial neoplasia will be eligible. Finally, subjects who are on hormonal therapy for a history of either prostate cancer or breast cancer may enroll, provided that there has been no evidence of disease progression during the previous three years.
- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
- Contraindication to any of the required concomitant drugs or supportive treatments or intolerance to hydration due to preexisting pulmonary or cardiac impairment including pleural effusion requiring thoracentesis or ascites requiring paracentesis.
- Known intolerance to carfilzomib.
- Co-administration with strong CYP3A4 inhibitors (such as, but not limited to, boceprevir, clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole) as well as fluconazole (a dual inhibitor of CYP3A4 and CYP2C9).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Levine Cancer Institute
Charlotte, North Carolina, 28204
Karmanos Cancer Institute
Detroit, Michigan, 48201
About this study
Official title: LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Phase I/II Study of Carfilzomib, Ruxolitinib, and Low Dose Dexamethasone for Carfilzomib-Refractory Multiple Myeloma
The primary objective of Phase I is to establish the maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and dexamethasone. The primary objective of phase II is to evaluate progression-free survival (PFS) at 4 months in multiple myeloma subjects who receive the combination treatment carfilzomib, dexamethasone, and ruxolitinib.
Read the detailed description
This is an open-label, Phase I/II study of carfilzomib, ruxolitinib, and low-dose dexamethasone for carfilzomib-refractory multiple myeloma. Phase I is designed to evaluate overall maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and dexamethasone in the following cohorts: Cohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib. Phase II is designed to evaluate 4-month progression-free survival (PFS) in the following cohorts: Cohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen. Up to 18 evaluable subjects will be enrolled in Phase I over approximately 12 months. An additional 30 evaluable subjects will be enrolled in Phase II over 24 months.
- Conditions
- Multiple Myeloma
- Being tested
- Carfilzomib, Ruxolitinib, Dexamethasone
- Keywords
- Plasma Cell Neoplasms, Blood Malignancy
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called Kyprolis
Irreversible proteasome inhibitor
RuxolitinibDrug
Also called Jakafi
Oral JAK inhibitor
DexamethasoneDrug
glucocorticoid
| Study group | Role | What they receive |
|---|---|---|
| Phase I | Experimental | Cohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib Receives: Drug: Carfilzomib; Drug: Ruxolitinib; Drug: Dexamethasone |
| Phase II | Other | Cohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen Receives: Drug: Carfilzomib; Drug: Ruxolitinib; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT)
DLTs will be determined for each subject as a binary variable indicating whether or not the subject experienced a DLT during Cycle 1
Measured: 28 days
Secondary outcomes (8)
Objective Response Rate (ORR)
Objective response will be determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of PR or better as per the IMWG criteria
Measured: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
Clinical Benefit Rate
Clinical benefit will be determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of minimal response (MR) or better as determined by the IMWG criteria
Measured: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
Disease Control Rate
Disease control will be determined for each subject as a binary variable indicating whether or not the subject achieved a disease response or stable disease for greater than or equal to 8 weeks
Measured: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
Progression-free Survival (PFS)
PFS is defined as the duration of time from the initiation of study treatment with ruxolitinib to first occurrence of either progressive disease or death without progressive disease.
Measured: approx. 5 years
Time to Best Response
Time to best response will be defined as the time from initiation of ruxolitinib treatment to the time of best objective status assessment of response.
Measured: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
Overall Survival
Overall survival is defined as the duration from initiation of ruxolitinib treatment to the date of death from any cause.
Measured: approx. 5 years
Time to Progression
Time to progression (TTP) is defined as the duration of time from the initiation of study treatment with ruxolitinib to first occurrence of either progressive disease or death.
Measured: approx. 5 years
Duration of Response
Duration of response will be defined as the time from first objective status assessment of response to the time of first documented disease progression or death.
Measured: approx. 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2018
- Study start3 Jan 2019
- Primary completion7 Nov 2022
- Study completion21 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation, Multiple Myeloma Research Consortium, Amgen
- Responsible party
- Sponsor
- Investigators
- Shebli Atrash, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03773107
- Sponsor's protocol ID
- IRB00081612
- Other IDs
- 00031040, LCI-HEM-MYE-CRD-004
- Status last verified
- Jan 2025
- First submitted
- 10 Dec 2018
- Last updated
- 13 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Phase I/II Study of Carfilzomib, Ruxolitinib, and Low Dose Dexamethasone for Carfilzomib-Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT03773107
- Acronym / sponsor ID
- IRB00081612
- Conditions
- Multiple Myeloma
- Keywords
- Plasma Cell Neoplasms, Blood Malignancy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Incyte Corporation, Multiple Myeloma Research Consortium, Amgen
- Study start
- 3 Jan 2019 (actual)
- Primary completion
- 7 Nov 2022 (actual)
- Study completion
- 21 Feb 2024 (actual)
- First posted
- 12 Dec 2018 (actual)
- Results
- Posted 5 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of Phase I is to establish the maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and dexamethasone. The primary objective of phase II is to evaluate progression-free survival (PFS) at 4 months in multiple myeloma subjects who receive the combination treatment carfilzomib, dexamethasone, and ruxolitinib.
Detailed description
This is an open-label, Phase I/II study of carfilzomib, ruxolitinib, and low-dose dexamethasone for carfilzomib-refractory multiple myeloma. Phase I is designed to evaluate overall maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and dexamethasone in the following cohorts: Cohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib. Phase II is designed to evaluate 4-month progression-free survival (PFS) in the following cohorts: Cohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen. Up to 18 evaluable subjects will be enrolled in Phase I over approximately 12 months. An additional 30 evaluable subjects will be enrolled in Phase II over 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase I | Experimental | Drug: Carfilzomib, Drug: Ruxolitinib, Drug: DexamethasoneCohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib |
| Phase II | Other | Drug: Carfilzomib, Drug: Ruxolitinib, Drug: DexamethasoneCohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Documented history of relapsed and/or refractory multiple myeloma with > 2 lines of therapy. One of the prior lines of therapy must have been a carfilzomib containing regimen with evidence of relapse or progression within the last 60 days of the carfilzomib containing regimen with a carfilzomib dose of at least 27 mg/m2. Carfilzomib containing regimen at the standard dose of 20/27 mg/m2 is acceptable.
- Measurable disease, as defined by at least one of the following:
- Adequate bone marrow reserves, as defined by the following:
- Adequate hepatic function, as defined by the following:
- Adequate renal function, as defined by the following: creatinine clearance (CrCl) ≥ 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula.
Key exclusion criteria (15 listed)
- Non-secretory multiple myeloma
- Known amyloidosis
- Known POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Clinically significant illness including, but not limited to the following: active systemic infection, uncontrolled hypertension (as defined by BP > 160/90), New York Heart Association Class III and IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months of consent, uncontrolled cardiac arrhythmia, or any other condition (including laboratory abnormalities) that, in the opinion of the Investigator, places the subject at unacceptable risk for adverse outcome if he/she were to participate in the study
- Prior cerebrovascular accident with persistent neurologic deficit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarfilzomibAlso: KyprolisIrreversible proteasome inhibitor | Drug | Phase I, Phase II |
| RuxolitinibAlso: JakafiOral JAK inhibitor | Drug | Phase I, Phase II |
| Dexamethasoneglucocorticoid | Drug | Phase I, Phase II |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: 28 days
DLTs will be determined for each subject as a binary variable indicating whether or not the subject experienced a DLT during Cycle 1
8 secondary outcomes
Objective Response Rate (ORR)
Time frame: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
Clinical Benefit Rate
Time frame: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
Disease Control Rate
Time frame: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
Progression-free Survival (PFS)
Time frame: approx. 5 years
Time to Best Response
Time frame: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
Overall Survival
Time frame: approx. 5 years
Time to Progression
Time frame: approx. 5 years
Duration of Response
Time frame: approx. 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shebli Atrash, MD principal investigator
Wake Forest University Health Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Carfilzomib, Ruxolitinib and Dexamethasone in people with Multiple Myeloma, run by Wake Forest University Health Sciences at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (DLT) (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2025.